Precipitation processes as described above are known in the art and are typically used to produce nano- and microparticles, i.e. particles with average diameters that are typically in the range of 100 nm to 80 μm.
It has been suggested in the prior art to employ the aforementioned precipitation process for the preparation of particles containing an active ingredient dispersed in a carrier material. DE-A 37 44 329 describes a process for the preparation of a composition comprising an active ingredient, e.g. a pharmaceutically active substance, and a carrier material in which a liquid containing the active ingredient and the carrier material is contacted with a fluid gas, e.g. supercritical carbon dioxide; the liquid is extracted by the fluid gas and the composition containing the active ingredient and the carrier material is recovered in the form of small particles. This process offers the advantage that it enables the manufacture of preparations that do not contain solvent residues or that contain solvent residues in toxicologically harmless amounts.
WO 2004/04862 describes a method of producing particles comprising contacting an emulsion with a supercritical fluid, the emulsion having a continuous phase and a discontinuous phase, the discontinuous phase comprising a solvent having a solute dissolved therein, the solute being generally insoluble in the continuous phase, and the solvent in the discontinuous phase being soluble in the supercritical fluid; and extracting the solvent from the discontinuous phase of the emulsion and into the supercritical fluid to precipitate the solute and thereby form particles of solute suspended in the continuous phase. The solute is preferably a substance that is insoluble or slightly soluble in water. The discontinuous phase is typically an organic solvent or an oil. The continuous phase is preferably water. The method described in WO 2004/04862 can yield particles of solute having a high purity and a narrow particle size distribution. These particles may be isolated from the continuous phase in which they are suspended by means of ultra-filtration or high-speed centrifugation.
The above mentioned processes are less suitable for producing particles containing active ingredients that are very sensitive, e.g. ingredients whose activity is adversely affected by exposure to oxygen, light, moisture, heat and/or friction. Furthermore, upon application, the particles produced by the above methods will instantaneously start releasing the active ingredients contained therein whereas it is often desirable that such release occurs with a certain delay.